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Review

Glycosylation and Its Role in Immune Checkpoint Proteins: From Molecular Mechanisms to Clinical Implications

Department of General Surgery, Rui** Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200000, China
*
Author to whom correspondence should be addressed.
Biomedicines 2024, 12(7), 1446; https://doi.org/10.3390/biomedicines12071446
Submission received: 16 May 2024 / Revised: 21 June 2024 / Accepted: 22 June 2024 / Published: 28 June 2024
(This article belongs to the Section Immunology and Immunotherapy)

Abstract

Immune checkpoint proteins have become recent research hotspots for their vital role in maintaining peripheral immune tolerance and suppressing immune response function in a wide range of tumors. Therefore, investigating the immunomodulatory functions of immune checkpoints and their therapeutic potential for clinical use is of paramount importance. The immune checkpoint blockade (ICB) is an important component of cancer immunotherapy, as it targets inhibitory immune signaling transduction with antagonistic antibodies to restore the host immune response. Anti-programmed cell death-1 (PD-1) and anti-cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) monoclonal antibodies are two main types of widely used ICBs that drastically improve the survival and prognosis of many patients with cancer. Nevertheless, the response rate of most cancer types remains relatively low due to the drug resistance of ICBs, which calls for an in-depth exploration to improve their efficacy. Accumulating evidence suggests that immune checkpoint proteins are glycosylated in forms of N-glycosylation, core fucosylation, or sialylation, which affect multiple biological functions of proteins such as protein biosynthesis, stability, and interaction. In this review, we give a brief introduction to several immune checkpoints and summarize primary molecular mechanisms that modulate protein stability and immunosuppressive function. In addition, newly developed methods targeting glycosylation on immune checkpoints for detection used to stratify patients, as well as small-molecule agents disrupting receptor–ligand interactions to circumvent drug resistance of traditional ICBs, in order to increase the clinical efficacy of immunotherapy strategies of patients with cancer, are also included to provide new insights into scientific research and clinical treatments.
Keywords: immunotherapy; immune checkpoint; glycosylation; sialylation; PD-L1; siglecs immunotherapy; immune checkpoint; glycosylation; sialylation; PD-L1; siglecs

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MDPI and ACS Style

Liu, J.; Xu, X.; Zhong, H.; Yu, M.; Abuduaini, N.; Zhang, S.; Yang, X.; Feng, B. Glycosylation and Its Role in Immune Checkpoint Proteins: From Molecular Mechanisms to Clinical Implications. Biomedicines 2024, 12, 1446. https://doi.org/10.3390/biomedicines12071446

AMA Style

Liu J, Xu X, Zhong H, Yu M, Abuduaini N, Zhang S, Yang X, Feng B. Glycosylation and Its Role in Immune Checkpoint Proteins: From Molecular Mechanisms to Clinical Implications. Biomedicines. 2024; 12(7):1446. https://doi.org/10.3390/biomedicines12071446

Chicago/Turabian Style

Liu, **gyi, **mo Xu, Hao Zhong, Mengqin Yu, Naijipu Abuduaini, Sen Zhang, **ao Yang, and Bo Feng. 2024. "Glycosylation and Its Role in Immune Checkpoint Proteins: From Molecular Mechanisms to Clinical Implications" Biomedicines 12, no. 7: 1446. https://doi.org/10.3390/biomedicines12071446

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